Characteristics of cardiac injury complicating with acute kidney injury and mortality risk in coronavirus disease 2019 (COVID-19) patients

Objectives: This study aimed to identify the clinical features of cardiac injury complicating with acute kidney injury (AKI) and its risk for a fatal outcome in patients infected with coronavirus disease 2019 (COVID-19) pneumonia. Methods: Initial signs and symptoms and clinical laboratory, radiological, and treatment information were obtained from seven hospitals in China from January 23, 2020, to March 15, 2020. Results: Of 438 patients, 36 (8.22%) displayed isolated cardiac injury, 17 (3.88%) had isolated AKI, and 17 (3.88%) displayed cardiac injury complicating with AKI. Compared with patients without cardiac injury or AKI, patients with isolated cardiac injury, isolated AKI, and cardiac injury complicating with AKI were older (55, 65, 74 vs. 48 years, P < 0.0001) and critically severe. More patients displayed fatigue, dyspnea, and comorbidities in the group with cardiac injury complicating with AKI. Moreover, the indexes reflecting myocardial, renal, liver, and coagulation dysfunctions and infection-related factors were significantly different among the four groups. After adjustment for covariates, patients with cardiac injury complicating with AKI had a higher hazard ratio for mortality (6.64;95% confidence interval, 1.51–29.30). Conclusion: Cardiac injury complicating with kidney injury significantly increased the risk for in-hospital mortality in COVID-19 pneumonia patients. Therefore, early detection at admission and careful monitoring of myocardial and renal injury through biomarkers during hospitalization is recommended to reduce the harm to patients.

Mortality risk analysis for patients with severe coronavirus disease 2019 pneumonia

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is currently a global pandemic. Information about predicting mortality in severe COVID-19 remains unclear. METHODS: A total of 151 COVID-19 in-patients from January 23 to March 8, 2020, were divided into severe and critically severe groups and survival and mortality groups. Differences in the clinical and imaging data between the groups were analyzed. Factors associated with COVID-19 mortality were analyzed by logistic regression, and a mortality prediction model was developed. RESULTS: Many clinical and imaging indices were significantly different between groups, including age, epidemic history, medical history, duration of symptoms before admission, routine blood parameters, inflammatory-related factors, Na+, myocardial zymogram, liver and renal function, coagulation function, fraction of inspired oxygen and complications. The proportions of patients with imaging Stage III and a comprehensive computed tomography score were significantly increased in the mortality group. Factors in the prediction model included patient age, cardiac injury, acute kidney injury, and acute respiratory distress syndrome. The area under the receiver operating characteristic curve of the prediction model was 0.9593. CONCLUSIONS: The clinical and imaging data reflected the severity of COVID-19 pneumonia. The mortality prediction model might be a promising method to help clinicians quickly identify COVID-19 patients who are at high risk of death.

Discovery of drugs to combat covid-19 inspired by traditional Chinese medicine.

Contributions from traditional knowledge and history have proven useful in recent years to advance drug discovery. In response to the emergence of covid-19, scientists revisited traditional Chinese medicine. This source of inspiration for drugs to treat this new disease is described here at three different levels: traditional Chinese medicinal herbs, traditional Chinese medical formulas, and traditional Chinese medical texts. Drug discovery inspired by traditional Chinese medicine still faces serious resistance for various reasons, including its system of formulas and clinical trial design. A perspective that includes related issues would benefit the reasonable application of traditional knowledge in drug research and development.

Anti-SARS-CoV-2 spike immunoglobulin G and immunoglobulin M titers decline as interval from the second inactivated vaccine dose to the onset of illness is prolonged in breakthrough infection patients.

BACKGROUND: Understanding of the early immune response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infections is limited. METHODS: Ninety-eight patients with coronavirus disease 2019 (COVID-19) breakthrough infections were divided into two groups, with intervals from receiving the second dose of inactivated vaccine to the onset of illness <60 or ≥60 days. RESULTS: The median lymphocyte count and the median anti-SARS-CoV-2 spike immunoglobulin G (IgG) and immunoglobulin M (IgM) titers were higher in the <60-day interval group compared with the corresponding medians in the ≥60-day interval group (p = 0.005, p = 0.001, and p = 0.001, respectively). The median interleukin-6 (IL-6) level in the <60-day interval group was significantly lower than the median IL-6 level in the ≥60-day interval group (p < 0.001). CONCLUSIONS: Our results highlight the different anti-SARS-CoV-2 spike IgG and IgM antibody titers among patients with different intervals from receiving the second dose of inactivated vaccine to the onset of illness.

Oral Liushen pill for patients with COVID-19: A prospective randomized controlled trial.

We examined the efficacy and safety of Liushen pill combined with basic treatment for patients with COVID-19. In total, 181 patients hospitalized with COVID-19, classified as asymptomatic mild type, were randomly divided into the experimental (n = 91) and control (n = 90) groups and were administered placebo (Maizao decoction) and Maizao decoction and Liushen pill, in addition to standard care, respectively. The negative conversion rate of nucleic acid (Day 7), hospital discharge rate (Days 8, 10, and 14), symptom disappearance rate (Days 3, 5, and 7), inflammatory cytokine levels, and adverse events were compared between the groups. The negative viral conversion rate was significantly higher in the experimental than in the control group (48.35 vs. 31.11%, p < 0.05). Subgroup analysis showed a similar significant trend when the Ct value was ≤30 at baseline. After 10 days, the hospital discharge rate was significantly higher in the experimental than in the control group (69.23 vs. 53.33%, p < 0.05). After 3-day medication, the headache symptoms significantly disappeared in the experimental (88.57%) compared to the control group (63.33%) (p < 0.05). After 5 days, the symptom disappearance rates of headache and cough were significantly higher in the experimental (97.14%) than in the control group (97.14 vs. 80.00, p < 0.05; 82.65 vs. 58.93%, p < 0.01, respectively). Posttreatment, the procalcitonin level was significantly lower in the experimental than in the control group (0.09 ± 0.00 vs. 0.14 ± 0.05 ng/L; p < 0.05). There were no significant between-group differences in clinical safety test indices. Early intervention with Liushen pill improved cough and headache and increased negative viral conversion and discharge rate.

Effect of liushen capsules (pill) on antiviral activity of COVID-19 in vitro and in patients with positive nucleic acid for more than 14 days

Objective To observe the efficacy and safety Liushen Capsules(Pill,LSP) combined with basic therapy on patients with coronavirus disease 2019(COVID-19) and positive nucleic acid for more than 14 days, and to test the in vitro antiviral effect of LSP. Methods To test the in vitro antiviral effect against the omicron(B.1.1.529) variant, its half-maximal inhibitory concentration(IC50) was determined by cytopathic effect test. The protocol was registered in Chinese Clinical Trial Registry(No. ChiCTR2200057532). Totally 50 patients who tested positive for severe acute respiratory syndrome coronavirus 2(SARSCoV-2), who were asymptomatic or had mild symptoms, were randomly divided into experimental group(26 cases) and control group(24 cases). The control group was given a basic treatment, and the experimental group was given LSP in conjunction with the basis treatment. The average negative time, negative conversion rate, immunological indices(IgG,IgM), and adverse events during treatment were compared between the two groups. Results The IC50 of LSP against SARS-CoV-2(omicron strain)was 0.194 8 g/mL. The average negative time of the virus in the experimental group [(5.03+or-2.41)d] was significantly lower than that in the control group [(6.46 +or-2.32)d,P<0.05]. After five days treatment, the negative conversion rate of the experimental group [57.36%(15/26)] was significantly lower than that of the control group [57.36%(15/26),P<0.05]. During the treatment, the negative conversion rate of the experimental group was always higher than that of the control group(P< 0.05). There was no significant difference in adverse reactions between the two groups(P>0.05). Conclusions LSP have an antiviral effect on SARS-CoV-2 in vitro, combined with basic therapy has certain curative effects on patients with positive nucleic acid for more than 14 days, and it can significantly shorten the negative conversion time of nucleic acid and negative rate, and improve the immune function of patients.

Comparison of the duration of viral RNA shedding and anti-SARS-CoV-2 spike IgG and IgM antibody titers in COVID-19 patients who were vaccinated with inactivated vaccines or not: a retrospective study.

BACKGROUND: At present, the role of inactivated vaccines in viral RNA shedding among Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) breakthrough infections is still unknown. METHODS: We collected data of 147 coronavirus disease 2019 (COVID-19) patients with mild-to-moderate illness who were hospitalized in the Third People's Hospital of Yangzhou from 7 to 20 August 2021 and analyzed the differences in symptoms and laboratory tests among fully vaccinated (FV), partially vaccinated (PV) and unvaccinated (UV) patients. RESULTS: The median duration of viral RNA shedding was shorter in the FV (12 [IQR, 9.5-14] days) and PV (13 [IQR, 9-16.75] days) groups than in the UV group (15 [IQR, 11.75-17.25] days) (adjusted P < 0.001 and adjusted P = 0.23, respectively). The median titers of SARS-CoV-2-specific IgG and IgM were significantly higher in the FV (12.29 S/co [IQR, 2.08-63.59] and 0.3 S/co [IQR, 0.05-2.29], respectively) and PV (0.68 S/co [IQR, 0.14-28.69] and 0.12 S/co [0.03-5.23], respectively) groups than in the UV group (0.06 S/co [IQR, 0.03-0.47] and 0.04 S/co [IQR, 0.02-0.07]) (adjusted P < 0.001 and adjusted P = 0.008, respectively). CONCLUSIONS: Inactivated vaccines may shorten viral RNA shedding in breakthrough infected patients who have mild-to-moderate illness and may improve the ability of the host to generate specific antibodies to infection.

The antiviral properties of tea

Tea (Camellia sinensis) is known as a global health beverage, and global tea consumption increases due to its biological activities. In the last 30 years. antiviral activities of tea and its components, especially tea polyphenols. with different modes of action were demonstrated on diverse families of viruses. such as influenza virus, coronavirus, hepatitis virus, and human immunodeficiency virus. etc. This review summarized the current knowledge on the antiviral activities of tea and its components. Most of these studies demonstrated antiviral properties of tea and its components by in vitro biochemical or cell experiments with little rodent and clinical studies. Therefore, it is still unclear whether the antiviral effects of daily tea consumption are available. More large-scale randomized intervention and epidemiological/clinical studies are needed to confirm clinical efficacy of tea and its components.

Ultrapotent neutralizing antibodies against SARS-CoV-2 with a high degree of mutation resistance.

Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22's only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2.

Application of Non-Invasive Ventilator in Treatment of Severe COVID-19 Patients.

BACKGROUND: Since December 2019, there has been a global outbreak of COVID-19. As of the end of July 2020, more than 600,000 deaths had been reported globally. The purpose of this paper is to further explore the application of non-invasive ventilation in severe COVID-19 patients. METHODS: A retrospective study was conducted to included 57 confirmed COVID-19 patients, among which 36 cases were severe. According to different oxygen inhalation methods, they were divided into non-invasive ventilator assisted ventilation group with 21 cases (group A) and 15 cases of nasal catheter oxygen inhalation group (group B). The data of respiration (RR), heart rate (HR), partial arterial pressure of oxygen (PaO2), partial arterial pressure of carbon dioxide (PaCO2), and oxygenation index (OI) before the treatment of noninvasive ventilator assisted ventilation or nasal catheter oxygen treatment at 24, 48, and 72 hours of treatment of the 2 groups were collected and analyzed to determine whether the above indicators were statistically different in each time period. RESULTS: After 24 hours of treatment with noninvasive ventilator assisted ventilation in group A, RR gradually decreased, PaO2 and OI were significantly higher than before treatment, while after 24 hours of treatment, PaO2, RR, HR and other indexes in group B showed no significant improvement, and OI increased gradually after 48 hours of treatment, with statistically significant difference compared with that before treatment. CONCLUSIONS: Early adoption of non-invasive ventilation can effectively improve the hypoxic state of patients with severe COVID-19. The combination of underlying diseases will not prolong the use of non-invasive ventilation.

Research progress of epigallocatechin-3-gallate (EGCG) on anti-pathogenic microbes and immune regulation activities.

At the end of 2019, the COVID-19 virus spread worldwide, infecting millions of people. Infectious diseases induced by pathogenic microorganisms such as the influenza virus, hepatitis virus, and Mycobacterium tuberculosis are also a major threat to public health. The high mortality caused by infectious pathogenic microorganisms is due to their strong virulence, which leads to the excessive counterattack by the host immune system and severe inflammatory damage of the immune system. This paper reviews the efficacy, mechanism and related immune regulation of epigallocatechin-3-gallate (EGCG) as an anti-pathogenic microorganism drug. EGCG mainly shows both direct and indirect anti-infection effects. EGCG directly inhibits early infection by interfering with the adsorption on host cells, inhibiting virus replication and reducing bacterial biofilm formation and toxin release; EGCG indirectly inhibits infection by regulating immune inflammation and antioxidation. At the same time, we reviewed the bioavailability and safety of EGCG in vivo. At present, the bioavailability of EGCG can be improved to some extent using nanostructured drug delivery systems and molecular modification technology in combination with other drugs. This study provides a theoretical basis for the development of EGCG as an adjuvant drug for anti-pathogenic microorganisms.

Specific cytokines in the inflammatory cytokine storm of patients with COVID-19-associated acute respiratory distress syndrome and extrapulmonary multiple-organ dysfunction.

BACKGROUND: To date, specific cytokines associated with development of acute respiratory distress syndrome (ARDS) and extrapulmonary multiple organ dysfunction (MOD) in COVID-19 patients have not been systematically described. We determined the levels of inflammatory cytokines in patients with COVID-19 and their relationships with ARDS and extrapulmonary MOD. METHODS: The clinical and laboratory data of 94 COVID-19 patients with and without ARDS were analyzed. The levels of inflammatory cytokines (interleukin 6 [IL-6], IL-8, IL-10, and tumor necrosis factor α [TNF-α]) were measured on days 1, 3, and 5 following admission. Seventeen healthy volunteers were recruited as controls. Correlations in the levels of inflammatory cytokines with clinical and laboratory variables were analyzed, furthermore, we also explored the relationships of different cytokines with ARDS and extrapulmonary MOD. RESULTS: The ARDS group had higher serum levels of all 4 inflammatory cytokines than the controls, and these levels steadily increased after admission. The ARDS group also had higher levels of IL-6, IL-8, and IL-10 than the non-ARDS group, and the levels of these cytokines correlated significantly with coagulation parameters and disseminated intravascular coagulation (DIC). The levels of IL-6 and TNF-α correlated with the levels of creatinine and urea nitrogen, and were also higher in ARDS patients with acute kidney injury (AKI). All 4 inflammatory cytokines had negative correlations with PaO2/FiO2. IL-6, IL-8, and TNF-α had positive correlations with the APACHE-II score. Relative to survivors, non-survivors had higher levels of IL-6 and IL-10 at admission, and increasing levels over time. CONCLUSIONS: The cytokine storm apparently contributed to the development of ARDS and extrapulmonary MOD in COVID-19 patients. The levels of IL-6, IL-8, and IL-10 correlated with DIC, and the levels of IL-6 and TNF-α were associated with AKI. Relative to survivors, patients who died within 28 days had increased levels of IL-6 and IL-10.

Clinical features and risk factors for severe-critically ill COVID-19 adult patients in Jiangsu, China: A multiple-centered, retrospective study.

ABSTRACT: Coronavirus disease 2019 (COVID-19) becomes a global pandemic in 2020. Early identification of severe ill patients is a top priority for clinicians. We aimed to describe clinical features and risk factors of severe-critically ill patients with COVID-19 in Jiangsu Province.This multi-centered retrospective study collected the information of 631 laboratory-confirmed COVID-19 patients hospitalized at 28 authorized hospitals in Jiangsu province from January 23, 2019 to March 13, 2020.A total of 583 adult patients with laboratory-confirmed COVID-19 were enrolled for final analysis, including 84 severe-critically ill patients and 499 mild-moderate patients. Median age of the severe-critically ill patients was 57.0 years old (interquartile range, 49.0-65.8), and 50 (59.5%) were males. Multisystemic laboratory abnormalities were observed on admission for severe-critically ill patients. These patients showed more noticeable radiologic abnormalities and more coexisting health issues as compared to the mild-moderate patients. Most of the severe-critically ill COVID-19 patients became deteriorated in 2 weeks after diagnosis. Age, D-dimer, and lymphocytes were independently associated with the progression of severe-critically illness.Older age, higher D-dimer levels and less lymphocyte counts on admission are potential risk factors for COVID-19 patients to develop into severe and critically illness.

Factors associated with delayed viral shedding in COVID-19 infected patients: A retrospective small-scale study.

BACKGROUND: The outbreak of COVID-19 has caused ever-increasing attention and public panic all over the world. Until now, data are limited about the risk factors to virus shedding in COVID-19 infected patients. METHODS: In this retrospective study, data were collected from 87 patients hospitalized with COVID-19 infection in Suzhou. Using Cox proportional hazards regression and Kaplan-Meier survival analysis, the risk factors to COVID-19 RNA shedding was to be established according to demographic information, clinical characteristics, epidemiological history, antiviral medicine and corticosteroid administration. RESULTS: The median duration of COVID-19 RNA shedding from admission was 13.11 ± 0.76 days. There was no significant difference in viral shedding duration in terms of gender, age, history of Hubei province stay, characteristics of chest CT on admission, lymphocytopenia and clinical severity. By Cox proportional hazards model, excessive 200 mg cumulative corticosteroid (HR, 3.425 [95% CI, 1.339-7.143]), time from illness onset to hospitalization (<5 days) (HR, 2.503 [95% CI, 1.433-4.371]) and arbidol-included therapy (HR, 2.073 [95% CI, 1.185-3.626]) were the independent risk factors to delay COVID-19 RNA shedding. Besides of excessive 200 mg of cumulative corticosteroid (HR, 2.825 [95% CI, 1.201-6.649]), admission within 5 days from illness onset (HR, 2.493 [95% CI, 1.393-4.462]) and arbidol-included therapy (HR, 2.102 [95% CI, 1.073-4.120]), lymphocytopenia (HR, 2.153 [95% CI, 1.097-4.225]) was further identified as another unfavorable factor to 10-day viral shedding. CONCLUSIONS: The potential risk factors could help clinicians to identify patients with delayed viral shedding, thereby providing the rational strategy of treatment and optimal anti-viral interventions.

Lung transplantation as therapeutic option in acute respiratory distress syndrome for coronavirus disease 2019-related pulmonary fibrosis.

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS: LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.

Phase 2a, open-label, dose-escalating, multi-center pharmacokinetic study of favipiravir (T-705) in combination with oseltamivir in patients with severe influenza.

BACKGROUND: The pharmacokinetics and appropriate dose regimens of favipiravir are unknown in hospitalized influenza patients; such data are also needed to determine dosage selection for favipiravir trials in COVID-19. METHODS: In this dose-escalating study, favipiravir pharmacokinetics and tolerability were assessed in critically ill influenza patients. Participants received one of two dosing regimens; Japan licensed dose (1600 mg BID on day 1 and 600 mg BID on the following days) and the higher dose (1800 mg/800 mg BID) trialed in uncomplicated influenza. The primary pharmacokinetic endpoint was the proportion of patients with a minimum observed plasma trough concentration (Ctrough) ≥20 mg/L at all measured time points after the second dose. RESULTS: Sixteen patients were enrolled into the low dose group and 19 patients into the high dose group of the study. Favipiravir Ctrough decreased significantly over time in both groups (p <0.01). Relative to day 2 (48 hrs), concentrations were 91.7% and 90.3% lower in the 1600/600 mg group and 79.3% and 89.5% lower in the 1800/800 mg group at day 7 and 10, respectively. In contrast, oseltamivir concentrations did not change significantly over time. A 2-compartment disposition model with first-order absorption and elimination described the observed favipiravir concentration-time data well. Modeling demonstrated that less than 50% of patients achieved Ctrough ≥20 mg/L for >80% of the duration of treatment of the two dose regimens evaluated (18.8% and 42.1% of patients for low and high dose regimen, respectively). Increasing the favipravir dosage predicted a higher proportion of patients reaching this threshold of 20 mg/L, suggesting that dosing regimens of ≥3600/2600 mg might be required for adequate concentrations. The two dosing regimens were well-tolerated in critical ill patients with influenza. CONCLUSION: The two dosing regimens proposed for uncomplicated influenza did not achieve our pre-defined treatment threshold.